We are interested in the synthesis and chemistry of new multifunctional compounds that contain the thiol ester of thiolactone groups together with other chemically reactive acylating or alkylating functions such as epoxide, aziridine or sulfonate ester groups as well as Michael accepting carbon-carbon double bonds and other unusual combinations. Several factors have raised our interest in the potential antineoplastic properties of multifunctional thiol esters and thiolactones. These groups are labile acylating functions that react readily with amine, mercaptan or other nucleophilic sites in proteins or nucleic acids. This reactivity would be increased still further in vivo as a result of metabolic activation by conversion to alpha-carbonyl sulfoxides by liver micromosal mixed function oxidases or related enzymes in other tissues. There are three major sections to our proposal: (1) Development of methods which will allow mild and specific introduction of alpha-alkylidene and alpha-methylene-gamma-thiobutyrolactone structural units into natural products of chemotherapeutic interest. (2) Development of novel, general synthetic procedures for the nucleophilic introduction of the thiol ester functon into complex molecules while seeking to avoid approaches that would bring about destruction of other labile groups that may also be present. (3) Investigation of methods for the preparation of the presently unknown thiol ester S-oxides (alpha-keto sulfoxides) anticipated as intermediates in the oxidative metabolism of thiol esters in animal systems.